During the past few years substantial progress has been made in unraveling how the genetic components that act to control sex determination and dosage compensation function together in a regulatory heirarchy. With the aim of understanding how this regulatory hierarchy functions at both the genetic and molecular levels our research is proceeding along three major lines. 1) A genetic analysis of known sex determination regulatory loci is being continued. 2) To extend our knowledge of this regulatory hierarchy to the molecular level, we have cloned and are characterizing the dsx locus with the initial aim of understanding the molecular basis for the active but opposite roles it plays in controlling sex determination in males and females. The tra, tra-2 and mle loci are also being cloned. 3) To fill in the gaps in our understanding of this regulatory hierarchy, we are screening for mutants at new regulatory loci. We have identified over 40 loci whose products are necessary for a normal mitotic chromosome cycle in D. melanogaster. The analysis of mutants at loci encoding essential cell cycle functions indicates that they specify a diverse array of products including ones required for: 1) condensation of all chromatin; 2) condensation of heterochromatin; 3) sister centromere cohesion; 4) spindle organization; 5) telomere separation; 6) separation of daughter nuclei; and 7) progression through interphase. Our primary focus will be on dissecting the processes of chromosome segregation and chromosome condensation. Extant mutants at 6 loci whose products are necessary for chromosome segregation are being analyzed by a variety of genetic, cytological (both light and electron microscopic) and molecular cloning techniques to define the functions of these genes. Extant mutants at 7 loci appear to be defective in functions necessary for chromatin condensation and are being analyzed genetically and biochemically. Other experiments include 1) using clones of cdc loci from yeast to identify homologous Drosophila functions and 2) examining how the events of the cell cycle are functionally and temporally coordinated.